Dynamic insights into research trends and trajectories in early reading: an analytical exploration via dynamic topic modeling.

Introduction: Early reading has gained significant attention in the academic community. With the increasing volume of literature on this subject, it has become crucial to assess the current research landscape and identify emerging trends. Methods: This study utilized the dynamic topic model to analyze a corpus of 1,638 articles obtained from the Web of Science Core Collection to furnish a lucid understanding of the prevailing research and forecast possible future directions. Results: Our in-depth assessment discerned 11 cardinal topics, among which notable ones were interventions' impacts on early reading competencies; foundational elements of early reading: phonological awareness, letters, and, spelling; and early literacy proficiencies in children with autism spectrum disorder. Although most topics have received consistent research attention, there has been a marked increase in some topics' popularity, such as foundational elements of early reading and early literary proficiencies in children with autism spectrum disorder. Conversely, other topics exhibited a downturn. Discussion: This analytical endeavor has yielded indispensable insights for scholars, decision-makers, and field practitioners, steering them toward pivotal research interrogatives, focal interest zones, and prospective research avenues. As per our extensive survey, this paper is a pioneering holistic purview of the seminal areas of early reading that highlights expected scholarly directions.

The Relation Between Attention and Memory.

The relation between attention and memory has long been deemed important for understanding cognition, and it was heavily researched even in the first experimental psychology laboratory by Wilhelm Wundt and his colleagues. Since then, the importance of the relation between attention and memory has been explored in myriad subdisciplines of psychology, and we incorporate a wide range of these diverse fields. Here, we examine some of the practical consequences of this relation and summarize work with various methodologies relating attention to memory in the fields of working memory, long-term memory, individual differences, life-span development, typical brain function, and neuropsychological conditions. We point out strengths and unanswered questions for our own embedded processes view of information processing, which is used to organize a large body of evidence. Last, we briefly consider the relation of the evidence to a range of other theoretical views before drawing conclusions about the state of the field.

Ir-Catalyzed Ortho-Selective C-H Borylation of Difluoromethyl Arenes.

The difluoromethyl group (CF2H) has received great attention due to its distinct properties in recent years. Herein, we report a new strategy for postmodification of difluoromethyl compounds. Ortho-selective C-H borylation of difluoromethyl arenes is achieved by a cyclometalated mesoionic carbene-Ir complex. The regioselectivity is controlled by a hydrogen bond between CF2H and the boryl group via the outer-sphere direction.

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia.

Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA. N-acetyl-L-cysteine (NAC, a reactive oxygen species scavenger) or exogenous EC infusion was administered to AA mice. Furthermore, the frequency and functions of BM ECs from AA patients and healthy donors were evaluated. BM ECs from AA patients were treated with NAC in vitro, and then the functions of BM ECs were evaluated. We found that BM ECs were significantly decreased and damaged in AA mice. Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized, whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice. Consistently, BM ECs in AA patients were decreased and dysfunctional. Furthermore, dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes, which could be repaired by NAC in vitro. The reactive oxygen species pathway was activated, and hematopoiesis- and immune-related signaling pathways were enriched in BM ECs of AA patients. In conclusion, our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA, suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.

Role of Escin in breast cancer therapy: potential mechanism for inducing ferroptosis and synergistic antitumor activity with cisplatin.

Breast cancer (BC) has threatened women worldwide for a long time, and novel treatments are needed. Ferroptosis is a new form of regulated cell death that is a potential therapeutic target for BC. In this study, we identified Escin, a traditional Chinese medicine, as a possible supplement for existing chemotherapy strategies. Escin inhibited BC cell growth in vitro and in vivo, and ferroptosis is probable to be the main cause for Escin-induced cell death. Mechanistically, Escin significantly downregulated the protein level of GPX4, while overexpression of GPX4 could reverse the ferroptosis triggered by Escin. Further study revealed that Escin could promote G6PD ubiquitination and degradation, thus inhibiting the expression of GPX4 and contributing to the ferroptosis. Moreover, proteasome inhibitor MG132 or G6PD overexpression could partially reverse Escin-induced ferroptosis, when G6PD knockdown aggravated that. In vivo study also supported that downregulation of G6PD exacerbated tumor growth inhibition by Escin. Finally, our data showed that cell apoptosis was dramatically elevated by Escin combined with cisplatin in BC cells. Taken together, these results suggest that Escin inhibits tumor growth in vivo and in vitro via regulating the ferroptosis mediated by G6PD/GPX4 axis. Our findings provide a promising therapeutic strategy for BC.

Ferritinophagy, a form of autophagic ferroptosis: New insights into cancer treatment.

Ferritinophagy, a form of autophagy, is also an important part of ferroptosis, a type of regulated cell death resulting from abnormal iron metabolism involving the production of reactive oxygen species. As ferroptosis, autophagy and cancer have been revealed, ferritinophagy has attracted increasing attention in cancer development. In this review, we discuss the latest research progress on ferroptosis, autophagy-associated ferroptosis led by ferritinophagy, the regulators of ferritinophagy and promising cancer treatments that target ferritinophagy. Ferritinophagy is at the intersection of ferroptosis and autophagy and plays a significant role in cancer development. The discussed studies provide new insights into the mechanisms of ferritinophagy and promising related treatments for cancer.

PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer.

The tumor recurrence and drug resistance of hepatocellular carcinoma (HCC) threatened patients a lot. The mechanism should be further explored. The information of expression status and survival were available in public databases. The Western blot and immunohistochemistry staining displayed the level of related proteins. CCK-8, colony-formation assays, transwell assay and wound healing assay were performed to illustrate the ability of tumor growth, invasion and migration. In vivo model was established to verify our cell experiments. In our study, we revealed that proteasome 26S subunit, non-ATPase 12 (PSMD12) was high expressed in HCC tissues and positive related to the survival. In vitro experiments suggested that PSMD12 knockdown attenuated tumor cell growth, invasion and migration. Moreover, PSMD12 interference blocked the activation of MEK-ERK pathway. The ERK inhibitor could alleviate the tumor-promoting effect in PSMD12-overexpression cells. In addition, kinesin family member 15 (KIF15) was also observed to be highly expressed in HCC and be harmful to the survival. The public database, the images of immunohistochemistry and the western blot illustrated that PSMD12 and KIF15 was positive correlated. KIF15 knockdown impaired tumor progression and tumor-promoting effect of PSMD12. The xenograft models supported the results of cell experiments. In conclusion, PSMD12 could activated MEK-ERK pathway via KIF15 upregulation, thereby promoting tumor progression.

High Glucose Accelerates Tumor Progression by Regulating MEDAG-Mediated Autophagy Levels in Breast Cancer.

Recent studies have shown that diabetes is a major risk factor for breast cancer (BC), but the mechanism is incompletely understood. Mesenteric estrogen-dependent adipogenesis (MEDAG) plays a significant role in both glucose uptake and BC development. However, the relationship between MEDAG and BC under high glucose (HG) conditions remains unclear. In our study, MEDAG expression was higher in BC tissue from diabetic patients than in BC tissue from nondiabetic patients. HG promoted BC progression in vitro and in vivo by upregulating MEDAG expression. Furthermore, MEDAG deficiency increased the autophagosome number and autophagic flux. Moreover, inhibition of autophagy partially reversed MEDAG knockdown (MEDAGKD)-induced suppression of tumorigenic biological behaviors and epithelial-mesenchymal transition (EMT) progression. Finally, MEDAG significantly suppressed AMPK phosphorylation. Additionally, the AMPK inhibitor Compound C markedly reduced autophagosome accumulation and antitumor effects in MEDAGKD cells. Treatment with the AMPK activator AICAR exhibited similar effects in MEDAG-overexpressing (MEDAGOE) cells. In conclusion, the MEDAG-AMPK-autophagy axis is vital to BC progression in diabetic patients. Our findings provide a novel treatment target for BC in patients with diabetes.

Buformin alleviates sepsis-induced acute lung injury via inhibiting NLRP3-mediated pyroptosis through an AMPK-dependent pathway.

BACKGROUND: NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated macrophage pyroptosis plays an important role in sepsis-induced acute lung injury (ALI). Inhibition of pyroptosis may be a way to alleviate inflammation as well as tissue damage triggered after lipopolysaccharide (LPS) stimulation. The aim of the present study was to explore whether buformin (BF), a hypoglycemic agent, could alleviate sepsis-induced ALI by inhibiting pyroptosis. METHODS: Wildtype C57BL/6 mice were randomly divided into control group, BF group, LPS group and LPS+BF group. BF group and LPS+BF group were pretreated with BF at a dose of 25 mg/kg, and the changes were observed. In addition, BF was used to interfere with THP-1 cells. The therapeutic effect of BF has been verified by intraperitoneal injection of BF in vivo after LPS stimulation. RESULTS: Inflammation and injury was significantly reduced in BF pretreated mice, and the indexes related to pyroptosis were suppressed. The phosphorylation of AMP-activated protein kinase (AMPK) in lung tissues of mice in the BF and LPS+BF groups was significantly higher. In THP-1 cells, the AMPK inhibitor, Compound C was added to demonstrate that BF worked via AMPK to inhibit NLRP3 inflammasome. It was further demonstrated that BF up-regulated autophagy, which in turn promoted NLRP3 inflammasome degradation. On the other hand, BF decreased NLRP3 mRNA level by increasing nuclear factor-erythroid 2 related factor 2 (Nrf2). And BF showed a therapeutic effect after LPS challenge. CONCLUSION: Our study confirmed that BF inhibited NLRP3-mediated pyroptosis in sepsis-induced ALI by up-regulating autophagy and Nrf2 protein level through an AMPK-dependent pathway. This provides a new strategy for clinical mitigation of sepsis-induced ALI.

Formation of ß-Lactoglobulin Self-Assemblies via Liquid-Liquid Phase Separation for Applications beyond the Biological Functions.

Proteins are like miracle machines, playing important roles in living organisms. They perform vital biofunctions by further combining together and/or with other biomacromolecules to form assemblies or condensates such as membraneless organelles. Therefore, studying the self-assembly of biomacromolecules is of fundamental importance. In addition to their biological activities, protein assemblies also exhibit extra properties that enable them to achieve applications beyond their original functions. Herein, this study showed that in the presence of monosaccharides, ethylene glycols, and amino acids, ß-lactoglobulin (ß-LG) can form assemblies with specific structures, which were highly reproducible. The mechanism of the assembly process was studied through multi-scale observations and theoretical analysis, and it was found that the assembling all started from the formation of solute-rich liquid droplets via liquid-liquid phase separation (LLPS). These droplets then combined together to form condensates with elaborate structures, and the condensates finally evolved to form assemblies with various morphologies. Such a mechanism of the assembly is valuable for studying the assembly processes that frequently occur in living organisms. Detailed studies concerning the properties and applications of the obtained ß-LG assemblies showed that the assemblies exhibited significantly better performances than the protein itself in terms of autofluorescence, antioxidant activity, and metal ion absorption, which indicates broad applications of these assemblies in bioimaging, biodetection, biodiagnosis, health maintenance, and pollution treatment. This study revealed that biomacromolecules, especially proteins, can be assembled via LLPS, and some unexpected application potentials could be found beyond their original biological functions.

Air Permeability, Shock Absorption Ability, and Flexural Strength of 3D-Printed Perforated ABS Polymer Sheets with 3D-Knitted Fabric Cushioning for Sports Face Guard Applications.

Sports face guards (FGs) are devices that protect athletes from maxillofacial injury or ensure rapid return to play following orofacial damage. Conventional FGs are uncomfortable to wear owing to stuffiness caused by poor ventilation and often slip off due to increase in weight due to absorption of moisture from perspiration, lowering players' performance. Herein, combinations of 3D-printed perforated acrylonitrile butadiene styrene (ABS) polymer sheets and 3D-knitted fabrics with honeycomb structures as cushioning materials were investigated to balance better wearing feel and mechanical properties. The flexural strength, weight, and shock absorption ability of, and air flow rate through, the ABS sheets with five different perforation patterns were evaluated and compared with those of conventional FG materials comprising a combination of polycaprolactone sheets for the medical splint and polychloroprene rubber for the cushioning material. The ABS sheets having 10% open area and 2.52 mm round holes, combined with knitted fabric cushioning, exhibited the requisite shock absorbing, higher air permeability, and lower weight properties than the conventional materials. Our results suggest that FGs fabricated using combinations of 3D-printed perforated ABS polymer sheets and 3D-knitted fabrics with honeycomb structures may impart enhanced wearing comfort for athletes.

Quantitative determination of mitophagy by fluorescence microscope.

Mitophagy is an evolutionally conserved cellular process that eliminates dysfunctional and excess mitochondria, thereby facilitating mitochondrial quality control and metabolic recycling. In addition, mitophagy is essential for cellular homeostasis and tissue development, and mitophagic dysfunction is related to various pathologies including neurodegenerative diseases and cancer. Thus, accurate quantitative measurement of mitophagy is one of the hot topics in the field of mitochondrial research. Fluorescence microscopical technology, one of the most widely used technologies at present, can well explain the occurrence and activity of mitophagy. Here, we introduce in detail an experimental method for the immunofluorescence-based quantitativ determination of mitophagy, which not only servers the in-depth study of mitochondrial homeostasis regulation, but also allows for the analyzing mitochondrial autophagy pathologies such as aging, neurodegenerative diseases and cancer.

Quantitative determination of autophagy flux by probes.

Macroautophagy is an intracellular degradation system in which autophagosomes and autolysosomes degrade the contents they contain in order to realize cell homeostasis and organelle renewal. Measuring autophagy activity and autophagic flux is very important for studying the role of autophagy, but accurate measurement of autophagic flux is quite complicated. Here, we use the GFP-mRFP-LC3 tandem probe to evaluate the cell autophagic flux. GFP is more sensitive to acidic environment and can be degraded in autolysosome due to the acidic environment. On the contrary, mRFP can be stably present in autolysosome due to its better tolerance to PH reduction. Hence, autophagic flux can be evaluated by calculating the ratio of GFP/RFP signal values. In addition, using this probe, we can more accurately measure the basal autophagic flux and induced autophagic flux in cells or animals. Summarily, the GFP-mRFP-LC3 tandem probe is a simple quantitative method to evaluate autophagic flux of cells and even whole organism.

Correction: Aung et al. Air Permeability, Shock Absorption Ability, and Flexural Strength of 3D-Printed Perforated ABS Polymer Sheets with 3D-Knitted Fabric Cushioning for Sports Face Guard Applications. Polymers 2021, 13, 1879.

Error in Figures 3 and 6 [...].

NRBP2 Functions as a Tumor Suppressor and Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer.

Nuclear Receptor Binding Protein 2 (NRBP2), one of the pseudokinases discovered during a screen of neural differentiation genes, inhibits tumor progression in medulloblastoma and hepatocellular carcinoma. However, the role and the mechanism of NRBP2 in the regulation of the progression of breast cancer (BC) have not been reported. In our study, NRBP2 was downregulated in human BC tissues compared with the corresponding normal tissues. Moreover, bioinformatics and cellular experiments illustrated that a lower level of NRBP2 contributed to a poor prognosis for patients with BC. In addition, we characterized the NRBP2-overexpressing BC cells and found that NRBP2 overexpression dramatically suppressed cell proliferation and invasion and inhibited the epithelial-mesenchymal transition (EMT) in cells in vitro, whereas knockdown of NRBP2 reversed these effects. Furthermore, overexpression of NRBP2 in the orthotopic breast tumor model significantly reduced lung metastatic nodules in nude mice. Mechanistically, NRBP2 regulated the activation of the 5'-adenosine monophosphate (AMP)-activated protein kinase/ mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Moreover, the inhibition of cell proliferation, invasion and the EMT by NRBP2 overexpression was partially rescued after treatment with an AMPK inhibitor. Conversely, mTOR-specific inhibitors eliminated the effects of NRBP2 knockdown on increasing cell proliferation, invasion and the EMT, which suggested the anti-tumor effect of NRBP2, which may be partially related to the regulation of the AMPK/mTOR pathway. Taken together, NRBP2, a novel and effective prognostic indicator, inhibited the progression of BC and may become a potential therapeutic target for BC.

Dual-demodulation large-scope high-sensitivity refractive index sensor based on twin-core PCF.

In this paper, a refractive index (RI) sensor based on the twin-core photonic crystal fiber (TC-PCF) is presented. Introducing the rectangular array in the core area makes the PCF possible to obtain high birefringence and low confinement loss over the wavelength range from 0.6 µm to 1.7 µm. Therefore, the core region can enhance the interaction between the core mode and the filling material. We studied theoretically the evolution characteristics of the birefringence and operating wavelength corresponding to the strongest polarization point under the condition of filling the rectangular array with RI matching fluid range from 1.33 to 1.41. Simulation results reveal that the proposed TC-PCF has opposite evolutions of change rates between the B and wavelength, and the maximum RI sensing sensitivities of 1.809×10-2 B/RIU and 8 700 nm/RIU at low and high RI infill are obtained respectively, which means that the TC-PCF features of dual-parameter demodulation for the RI sensing can maintain a high refractive index sensing sensitivity within a large scope of RI ranging from 1.33 to 1.41. Compared with the results of single-parameter demodulation, it is an optimized method to improve the sensitivity of low refractive index sensors, which has great application potency in the field of biochemical sensing and detection.

Exosomal microRNAs in cancer-related sarcopenia: Tumor-derived exosomal microRNAs in muscle atrophy.

Cancer-associated sarcopenia is a complex metabolic syndrome marked by muscle mass wasting. Muscle wasting is a serious complication that is a primary contributor to cancer-related mortality. The underlying molecular mechanisms of cancer-associated sarcopenia have not been completely described to date. In general, evidence shows that the main pathophysiological alterations in sarcopenia are associated with the degradation of cellular components, an exceptional inflammatory secretome and mitochondrial dysfunction. Importantly, we highlight the prospect that several miRNAs carried by tumor-derived exosomes that have shown the ability to promote inflammatory secretion, activate catabolism, and even participate in the regulation of cellular degradation pathways can be delivered to and exert effects on muscle cells. In this review, we aim to describe the current knowledge about the functions of exosomal miRNAs in the induction of cancer-associated muscle wasting and propose potential treatment strategies.

MEDAG enhances breast cancer progression and reduces epirubicin sensitivity through the AKT/AMPK/mTOR pathway.

Breast cancer (BC) is the most common malignancy among women. Mesenteric estrogen-dependent adipogenesis gene (MEDAG) was first reported as a novel adipogenic gene, and its involvement and mechanism in visceral adiposity were analyzed. However, the role of MEDAG in BC is unclear. The biological roles and corresponding mechanisms were investigated in vitro and in vivo. We found that MEDAG was highly expressed in BC samples and that a high MEDAG expression was correlated with clinicopathological characteristics and poor survival in BC patients. MEDAG knockdown inhibited cell proliferation, invasion, and migration; triggered epithelial-to-mesenchymal transition (EMT); and enhanced epirubicin sensitivity in vitro. The opposite results were observed in MEDAG-overexpressing cells. The inhibition of MEDAG suppressed tumor growth and metastasis in vivo. Mechanistically, MEDAG knockdown led to decreased phosphorylation levels of AKT, increased levels of p-AMPK, and reduced levels of p-mTOR, while the overexpression of MEDAG had the opposite effects. Moreover, the activation of p-AKT and inhibition of p-AMPK restored the effect of MEDAG on EMT and chemosensitivity in BC cell lines, indicating that MEDAG functions as an oncogene by regulating the AKT/AMPK/mTOR pathway. MEDAG regulates BC progression and EMT via the AKT/AMPK/mTOR pathway and reduces chemosensitivity in BC cells. Therefore, MEDAG is a promising target for BC.

NMIIA promotes tumorigenesis and prevents chemosensitivity in colorectal cancer by activating AMPK/mTOR pathway.

Non-muscle myosin IIA (NMIIA) has been reported to be involved in the carcinogenesis and malignant progression of various human tumors. However, the role and potential mechanism of NMIIA in the biological functions and apoptosis in colorectal cancer (CRC) remain elusive. In this study, we found that NMIIA was overexpressed in CRC tissues and significantly associated with poor survival in CRC patients. In addition, NMIIA promoted CRC cell proliferation and invasion via activating the AMPK/mTOR pathway in vitro, and NMIIA knockdown inhibited CRC growth in vivo. Meanwhile, NMIIA knockdown downregulated the CSCs markers (CD44 and CD133) expression in CRC cells. Furthermore, AMPK/mTOR pathway activation effectively reversed the NMIIA knockdown-induced inhibition of proliferation, invasion and stemness in CRC cells. Finally, NMIIA protects CRC cells from 5-FU-induced apoptosis and proliferation inhibition through the AMPK/mTOR pathway. Taken together, these results indicate that NMIIA plays a pivotal role in CRC growth and progression by regulating AMPK/mTOR pathway activation, and it may act as a novel therapeutic target prognostic factor in CRC.

The Role of T Lymphocytes in the Pathogenesis of Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell genetic mutation disease that causes defective erythrocyte membrane hemolysis. Its pathologic basis is the mutation of the PIG-A gene, whose product is necessary for the synthesis of glycosylphosphatidylinositol (GPI) anchors; the mutation of PIG-A gene results in the reduction or deletion of the GPI anchor, which leads to the deficiency of GPI-anchored proteins (GPI-APs), such as CD55 and CD59, which are complement inhibitors. The deficiency of complement inhibitors causes chronic complement-mediated intravascular hemolysis of GPI-anchor-deficient erythrocyte. PIG-A gene mutation could also be found in bone marrow hematopoietic stem cells (HSCs) of healthy people, but they have no growth advantage; only the HSCs with PIG-A gene mutation in PNH patients have this advantage and expand. Besides, HSCs from PIG-A-knockout mice do not show clonal expansion in bone marrow, so PIG-A mutation cannot explain the clonal advantage of the PNH clone and some additional factors are needed; thus, in recent years, many scholars have put forward the theories of the second hit, and immune escape theory is one of them. In this paper, we focus on how T lymphocytes are involved in immune escape hypothesis in the pathogenesis of PNH.